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Spatiotemporal resolution of the Ntla transcriptome in axial mesoderm development
Open accessAbstract
Transcription factors have diverse roles during embryonic development, combinatorially controlling cellular states in a spatially and temporally defined manner. Resolving the dynamic transcriptional profiles that underlie these patterning processes is essential for understanding embryogenesis at the molecular level. Here we show how temporal, tissue-specific changes in embryonic transcription factor function can be discerned by integrating caged morpholino oligonucleotides with photoactivatable fluorophores, fluorescence-activated cell sorting and microarray technologies. As a proof of principle, we have dynamically profiled No tail a (Ntla)-dependent genes at different stages of axial mesoderm development in zebrafish, discovering discrete sets of transcripts that are coincident with either notochord cell fate commitment or differentiation. Our studies reveal new regulators of notochord development and the sequential activation of distinct transcriptomes within a cell lineage by a single transcriptional factor and demonstrate how optically controlled chemical tools can dissect developmental processes with spatiotemporal precision.
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“Although zebrafish axial mesoderm has been well-characterized through mutagenesis screens, a role for Lhx1a in these developmental stages is likely to have gone unreported owing to the absence of gross morphological phenotypical changes at 10 hpf after disruption of lhx1a (ref. 49).”
From Dissecting cell identity via network inference and in silico gene perturbation (2023) · cites this paper as [49]
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Metadata
- Authors
- Shestopalov, I. A., Pitt, C. L. W., & Chen, J. K.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Chen, James K
- Venue
- Nature Chemical Biology
- Published
- 2012-01-29
- Volume
- 8
- Issue
- 3
- Pages
- 270-276
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC3288381
- OpenAlex
- W2075201827
- Cited by
- 42
- References
- 38
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 7 · 2013: 5 · 2012: 5
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DP1OD003792)
- National Institute of General Medical Sciences (R01GM072600, R01GM087292)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (DP1HD075622)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- notochord development, gene expression profiling, photoactivatable fluorophores, FACS cell isolation, transcription factor function, lineage commitment, cell lineage, zebrafish embryonic development, spatiotemporal gene expression
- MeSH terms
- Brachyury Protein, Animals, Fetal Proteins, Mesoderm, Time Factors, Zebrafish, Gene Expression Regulation, Developmental, T-Box Domain Proteins, Zebrafish Proteins, Transcriptome
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